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International audience; Ectomycorrhizal (ECM) fungi associate with the roots of woody plants in temperate and boreal forest, helping them to acquire water and nutrients. The molecular mechanisms responsible for these nutritional transfers are still poorly understood. The ECM fungus Hebeloma cylindrosporum expresses three H+:Pi symporters (HcPT1.1, HcPT1.2, and HcPT2) in extraradical and intraradical hyphae of ectomycorrhizae to transport phosphorus (P) from the soil to colonized roots. Since HcPT1.1 is only upregulated under low P conditions, we wondered whether an artificial overexpression of this transporter by a fungal Agrotransformation strategy could result in better P nutrition of the host plant Pinus pinaster. Surprisingly, we demonstrated that plants interacting with transgenic fungal lines overexpressing HcPT1.1 did not accumulate more P in their shoot compared to plants colonized with control isolates. Although the overexpression of HcPT1.1 did not affect the expression level of the other two P transporters in pure culture, a strong reduction of HcPT2 proteins in ectomycorrhizae, particularly in the hyphae internally colonizing roots, was observed by an immunolocalization approach. Our results revealed that the artificial overexpression of the P transporter HcPT1.1 strongly decreased the distribution of HcPT2 proteins in symbiotic structures, but still improved the P status of the host plant shoots compared to non-mycorrhizal plants. This suggests that a tight regulation and a functional redundancy between the H+:Pi symporters of H. cylindrosporum might exist to ensure a sustainable P delivery to P. pinaster roots.

This dissertation examines depictions of refugees in twenty-first-century German-language literature by Elfriede Jelinek, Jenny Erpenbeck, Navid Kermani, Maxi Obexer and Firas Alshater. Their selected works challenge stereotypical narratives about refugees as ‘undesirables,’ ‘invasive others,’ and ‘problems’ that threaten liberal nation-states in Europe. This study aims to illustrate how their texts convey that refugees are persons with many complex social identities rather than ‘invaders.’ My interdisciplinary methodology is based on three pillars: a mobility paradigm taken from human geography, a philosophical discussion of personhood, and notions of place derived from human geography and philosophy. I will show how interconnections between mobility, personhood, and place are relevant because refugees are adaptable persons in need of a new place (at least temporarily), but they experience a differential mobility compared to privileged migrants. First, the mobility paradigm enables a reading of literature that shows how current European Union asylum rules attempt to prevent displaced persons from accessing individual member country jurisdictions. As a result, refugees’ ability to physically move towards and within Europe is restricted. Second, literature can evoke philosophical ideas of personhood that illustrate detrimental effects when the label ‘refugee’ is repeatedly affixed to a displaced person’s life story. This label overrides all their past, present, and future experiences, and it unjustly portrays them as ‘problems’ or ‘undesirables’ rather than resourceful and capable individuals. Third, literature can reflect how places are shaped, maintained, and continually changed because social relations, experiences, and understandings intersect in persons’ life narratives. The findings of my interdisciplinary study are relevant for literary discourses on the categorization of migrants and on current European Union politics that support the free flow of goods and money but undermine the arrival of those in need of refuge.

Additional file 3. Changes on standard blood counts and the cellular immune status after continuous and interval exercise. Peripheral blood samples of healthy donors (n = 12) were analysed by flow cytometry at different time points before and after a single 30 min continuous (CONT) or interval (HIT) exercise (before, directly after, 1 h after and 24 h after exercise). Determined frequencies of CD45+ leukocytes, CD14+ monocytes, CD19+ B cells, CD3+/CD56+ NKT cells, and CD3−/CD56+ NK cells with their bright and dim subsets are displayed as normalized frequencies. Data are mean ± SD.

Additional file 4. Changes in standard blood counts after continuous and interval exercise differentiating between moderately and highly fit donors. Peripheral blood samples of healthy donors (n = 12) were analysed using a haemocytometer at different time points before and after a single 30 min continuous (CONT) or interval (HIT) exercise (before, directly after, 1 h after and 24 h after exercise). Donors were grouped according to their fitness level (moderate, n = 8, and high, n = 4, tested with the International Physical Activity Questionnaire, IPAQ). (A) Lymphocyte, granulocyte, and monocyte frequency is shown as percentage of the total leukocyte count. (B) White blood cell (WBC), lymphocyte, granulocyte, and monocyte counts are shown as absolute counts (×103/µl blood). Data are shown as mean ± SD.

Background: Immunosuppressive therapy or T-cell depletion in transplant patients can cause uncontrolled growth of Epstein-Barr virus (EBV)-infected B cells resulting in post-transplant lymphoproliferative disease (PTLD). Current treatment options do not distinguish between healthy and malignant B cells and are thereby often limited by severe side effects in the already immunocompromised patients. To specifically target EBV-infected B cells, we developed a novel peptide-selective chimeric antigen receptor (CAR) based on the monoclonal antibody TÜ165 which recognizes an Epstein-Barr nuclear antigen (EBNA)-3C-derived peptide in HLA-B∗35 context in a T-cell receptor (TCR)-like manner. In order to attract additional immune cells to proximity of PTLD cells, based on the TÜ165 CAR, we moreover generated T cells redirected for universal cytokine-mediated killing (TRUCKs), which induce interleukin (IL)-12 release on target contact. Methods: TÜ165-based CAR-T cells (CAR-Ts) and TRUCKs with inducible IL-12 expression in an all-in-one construct were generated. Functionality of the engineered cells was assessed in co-cultures with EBNA-3C-peptide-loaded, HLA-B∗35-expressing K562 cells and EBV-infected B cells as PTLD model. IL-12, secreted by TRUCKs on target contact, was further tested for its chemoattractive and activating potential towards monocytes and natural killer (NK) cells. Results: After co-cultivation with EBV target cells, TÜ165 CAR-Ts and TRUCKs showed an increased activation marker expression (CD137, CD25) and release of proinflammatory cytokines (interferon-gand tumor necrosis factor-a). Moreover, TÜ165 CAR-Ts and TRUCKs released apoptosis-inducing mediators (granzyme B and perforin) and were capable to specifically lyse EBV-positive target cells. Live cell imaging revealed a specific attraction of TÜ165 CAR-Ts around EBNA-3C-peptide-loaded target cells. Of note, TÜ165 TRUCKs with inducible IL-12 showed highly improved effector functions and additionally led to recruitment of monocyte and NK cell lines. Conclusions: Our results demonstrate that TÜ165 CAR-Ts recognize EBV peptide/HLA complexes in a TCR-like manner and thereby allow for recognizing an intracellular EBV target. TÜ165 TRUCKs equipped with inducible IL-12 expression responded even more effectively and released IL-12 recruited additional immune cells which are generally missing in proximity of lymphoproliferation in immunocompromised PTLD patients. This suggests a new and promising strategy to specifically target EBV-infected cells while sparing and mobilizing healthy immune cells and thereby enable control of EBV-associated lymphoproliferation.

Additional file 7. Effects of a single continuous and interval exercise on CD8+ T-cell cholesterol and activation levels in a donor-related setting. Peripheral blood samples of healthy donors (n = 5) were analysed at different time points before and after a single 30 min continuous (CONT) or interval (HIT) exercise (before, directly after, 1 h after and 24 h after exercise) to (A) quantify the level of cholesterol (µM)/1 × 106 cells (Amplex Red Cholesterol Assay Kit) and (B) to obtain the expression of CD69 on CD8+ T cells (flow cytometry). Data are shown in a donor-related setting as mean ± SD. Statistically significant difference is indicated by (*p

Additional file 1. Representative flow cytometric plots. Representative flow cytometry plots illustrating the gating strategy used to analyse (A) the cellular immune status in whole blood sample on a single-cell platform using TruCount tubes, (B) the enrichment efficiency of IFN-γ+ VSTs selected from PBMCs using the IFN-γ cytokine secretion assay, and (C) the activation level of isolated CD8+ T cells using CD69 as specific marker before and after exercise.

Additional file 5. Effects of a single continuous and interval exercise on stress, proliferation markers, T-cell cytotoxicity and parameters of cellular age. Peripheral blood samples of healthy donors (n = 12) were analysed at different time points before and after a single 30 min continuous (CONT) or interval (HIT) exercise (before, directly after, 1 h after and 24 h after exercise) using real-time PCR for quantification of (A) HSP70- and Ki67-, IFN-γ-, and granzyme B-mRNA levels. Constitutively expressed GAPDH gene was used as the reference standard for normalization of mRNA levels. RQ values were calculated by the delta–delta CT method. (B) Blood samples were further analysed regarding p16 levels, telomere ratio and telomere base pairs. Results are displayed as RQ, with the value from before exercise being the base line, and shown as mean ± SD.

Additional file 6. Impact of a single continuous and interval exercise on antigen-specific T-cell responses. Peripheral blood samples of healthy donors (n = 12) were analysed separately with the two-sample t approach adjusting for period at different time points before and after a single 30 min continuous (CONT) or interval (HIT) exercise (before, directly after, 1 h after and 24 h after exercise). Isolated PBMCs were stimulated overnight with CMV-, EBV- and AdV-specific peptide pools (CMV pp65, CMV IE1, EBV EBNA1, and EBV Consensus, AdV5 Hexon, and AdV5 Penton) and frequencies of functional-active virus-specific T cells were determined by IFN-γ EliSpot assay as spots per 1000 CD3+ T cells

Post-transplant lymphoproliferative disease (PTLD) represents a serious complication following allogeneic hematopoietic stem cell transplantation (alloHSCT). Previously, survival rates of PTLD have improved due to the introduction of rituximab. However, reports on curative management of refractory PTLD are scarce. Today, there is no consensus how to treat rituximab-refractory PTLD, especially in highly aggressive disease. Here, we describe successful management of refractory EBV-associated PTLD, specifically DLBCL, with combined brentuximab vedotin and third-party EBV-specific T-cells in a multidisciplinary treatment approach.

Post-transplant lymphoproliferative disease (PTLD) represents a serious complication following allogeneic hematopoietic stem cell transplantation (alloHSCT). Previously, survival rates of PTLD have improved due to the introduction of rituximab. However, reports on curative management of refractory PTLD are scarce. Today, there is no consensus how to treat rituximab-refractory PTLD, especially in highly aggressive disease. Here, we describe successful management of refractory EBV-associated PTLD, specifically DLBCL, with combined brentuximab vedotin and third-party EBV-specific T-cells in a multidisciplinary treatment approach. CA extern